We are particularly, but not exclusively, interested in developing information that wll improve drug therapy for hypertension and its sequelae, myocardial infarction and arrhythmias. MAJOR AREAS OF RESEARCH INCLUDE: 1) studies of the relative contributions of parent drug, drug metabolites, and reactive drug intermediates to the therapeutic and toxic effects of drugs in man and lab animals; this approach involves a detailed description of the distribution, metabolism, and mechanism of action of the drug coupled with efforts to modify therapeutic and toxic effects by pharmacological manipulation of specific pathways of drug distribution, transport and metabolism, first in animals then in man, e.g., beta-blocking, antiarrhythmic, antihypertensive and other drugs; 2) the central nervous system as a site for hypotensive drug action; 3) prophylactic therapy for myocardial infarction; 4) the role of prostaglandins in ganglion cell function, antihypertensive and diuretic drug action; 5) the pharmacological control of kallikrein-kinin; 6) the molecular basis of drug toxicity for chemicals and drugs that produce hepatic necrosis, hemolytic anemia and blood dyscrasias, including the development of models for the study of idiosyncratic drug reactions; 7) the biochemistry of polyamines in normal and disease states; and 8) the development of new and improved analytical techniques for the study of drugs and biochemicals. Independent and interdependent clinicians, pharmacologists, biochemists, toxicologists, organic and analytical chemists and engineers are working together studying at levels of biological organization ranging from artificial plasma, through subcellular fractions, cell suspensions, cell culture, isolated organs, laboratory animals to patients. The hospital and bench laboratory function as a continuum for study when possible. Core facilities (including a clinical research unit, outpatient research clinic and mass spectrometry laboratory with electron impact and chemical ionization capability) promote collaboration. BIBLIOGRAPHIC REFERENCES: Bagwell, E.E., T. Walle and J.K. Pruett: Efficacy of the N-acetyl metabolite of procainamide in reversing arrhythmias induced by coronary ligation in the dog. The Pharmacologist, 17 (2) Fall 1975. Pruett, J.K., T. Walle and E.E. Bagwell: Correlation of propranolol (Text Truncated - Exceeds Capacity)